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Biomedical subjects

A D Patel

Publications and source records attributed to A D Patel.

31 records · Page 2Linked to original sources

Processing prosodic and musical patterns: a neuropsychological investigation.

To explore the relationship between the processing of melodic and rhythmic patterns in speech and music, we tested the prosodic and musical discrimination abilities of two "amusic" subjects who suffered from music perception deficits secondary to bilateral brain damage. Prosodic discrimination was assessed with sentence pairs where members of a pair differed by intonation or rhythm, and musical discrimination was tested using musical-phrase pairs derived from the prosody of the sentence pairs. This novel technique was chosen to make task demands as comparable as possible across domains. One amusic subject showed good performance on both linguistic and musical discrimination tasks, while the other had difficulty with both tasks. In both subjects, level of performance was statistically similar across domains, suggesting shared neural resource for prosody and music. Further tests suggested that prosody and music may overlap in the processes used to maintain auditory patterns in working memory.

Adult↗

Processing syntactic relations in language and music: an event-related potential study.

In order to test the language-specificity of a known neural correlate of syntactic processing [the P600 event-related brain potential (ERP) component], this study directly compared ERPs elicited by syntactic incongruities in language and music. Using principles of phrase structure for language and principles of harmony and key-relatedness for music, sequences were constructed in which an element was either congruous, moderately incongruous, or highly incongruous with the preceding structural context. A within-subjects design using 15 musically educated adults revealed that linguistic and musical structural incongruities elicited positivities that were statistically indistinguishable in a specified latency range. In contrast, a music-specific ERP component was observed that showed antero-temporal right-hemisphere lateralization. The results argue against the language-specificity of the P600 and suggest that language and music can be studied in parallel to address questions of neural specificity in cognitive processing.

Adolescent↗

Ongoing immunologic activity after short courses of pulse cyclophosphamide in the NZB/W murine model of systemic lupus erythematosus.

OBJECTIVE: Short courses of intermittent pulse cyclophosphamide (CY) have mitigated ovarian toxicity but have also led to incomplete or unsustained remissions of active systemic lupus erythematosus (SLE) in many patients, prompting an evaluation of the immunologic effects of this regimen in the NZB/W female mouse (B/W) model of human SLE. METHODS: Phenotypic and functional characteristics of spleen lymphocytes from B/W mice treated with short courses of intraperitoneal (i.p.) CY were compared to those from untreated control B/W mice. RESULTS: After a single dose (250 mg/kg) of i.p. CY, spleen lymphocyte subpopulations fell abruptly but recovered within 4 weeks. Four monthly doses of i.p. CY (starting at 5 months of age) led to a sustained reduction in spleen lymphocyte subpopulations and a parallel decrease in the number of spleen cells spontaneously secreting immunoglobulin and anti-DNA antibody to about 30% of the number seen in untreated control B/W mice. Lipopolysaccharide induced secretion of total IgG and IgG anti-DNA by cultured spleen cells was not diminished one month after the 4 month course of i.p. CY. CONCLUSION: The 4 month course of i.p. CY produced a marked reduction in the number of activated B cells producing autoantibody, but did not achieve sustained immunomodulation judged by the unaltered proportion of spleen B cells spontaneously secreting immunoglobulin and anti-DNA, as well as the response to polyclonal activators of B cells. These results suggest a continued susceptibility to flares of SLE activity after brief courses of intensive immunosuppressive therapy.

Adjuvants, Immunologic↗

Differential requirement of protein tyrosine kinase and protein kinase C in the generation of IL-2-induced LAK cell and alpha CD3-induced CD3-AK cell responses.

This study examined the role of protein tyrosine kinase (PTK) and protein kinase C (PKC) in the signal transduction pathways for lymphocyte activation through IL-2R to generate LAK cells and through TCR-CD3 to generate CD3-AK cells. Two PTK inhibitors [herbimycin A and genistein (PTK-I)] and two PKC inhibitors [calphositin C and staurosporine (PKC-I)] were used in the experiments. It was found that the primary activation pathway through IL-2R was PTK-dependent; that is, generation of both the IL-2-induced proliferative and the cytotoxic responses was completely abrogated by PTK-I and not by PKC-I. Quite different results were obtained with the alpha CD3-induced CD3-AK cell response. First, the alpha CD3-induced proliferation was only partially inhibited by PTK-I or PKC-I alone. Second, generation of CD3-AK cytotoxic response was primarily PKC-dependent; that is, only PKC-I induced significant inhibition. Genistein was found to reduce protein tyrosine phosphorylation in both LAK cells and CD3-AK cells, indicating that CD3-AK cells were also susceptible to PTK-I treatment. Further studies showed that PTK-I and not PKC-I suppressed perforin mRNA expression and N-2-benzyoxycarbonyl-L-lysine thiobeneylester esterase production in LAK cells, and the opposite was true for CD3-AK cells. These results indicate that different pathways were employed in lymphocyte activation through IL-2R and TCR-CD3. The former pathway is primarily PTK-dependent. Activation through TCR-CD3 is a more complex event.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗

External fixator pin placement in the forearm: how safe is it? An anatomical study.

An anatomical study was undertaken using cadaveric forearms to identify the best technique and angle of pin placement for external fixator pins. We have found that inserting pins through stab incisions risks transfixion of the underlying structures and leads to an increased morbidity. We conclude that inserting pins under direct vision is much safer and that the optimum angle of pin insertion is in the coronal plane, parallel to the plane of the metacarpals.

Bone Nails↗

Fixation of intertrochanteric fractures of the femur. A randomised prospective comparison of the gamma nail and the dynamic hip screw.

We have prospectively compared the fixation of 100 intertrochanteric fractures of the proximal femur in elderly patients with random use of either a Dynamic Hip Screw (DHS) or a new intramedullary device, the Gamma nail. We found no difference in operating time, blood loss, wound complications, stay in hospital, place of eventual discharge, or the patients' mobility at final review. There was no difference in failure of proximal fixation: cut-out occurred in three cases with the DHS, and twice with the Gamma nail. However, in four cases fracture of the femur occurred close to the Gamma nail, requiring further major surgery. In the absence of these complications, union was seen by six months in both groups.

Aged↗

Interactions between murine B lymphocyte surface membrane molecules. Loaded but not free receptors for complement and the Fc portion of IgG co-cap independently with cross-linked surface Ig.

We have investigated the possible physical interactions between CR, receptors for the Fc gamma R and surface Ig (sIg) on the surface membrane of murine B lymphocytes. We used the rat mAb to murine CR, 8C12, and 7G6, as CR ligands, and soluble Ag-antibody complexes as FcR ligands; and F(ab')2 fragments of rabbit antibodies specific for mouse IgM and IgD as sIg ligands. We have found that: 1) sIg, CR, and Fc gamma R are not directly linked, because capping of any one did not affect the expression of the others; 2) the mAb 8C12 and 7G6 failed by themselves to cross-link CR; 3) soluble Ag-antibody complexes crosslinked some, Fc gamma R on a minority of Fc gamma R+ lymphocytes; 4) once loaded with anti-CR mAb, CR co-capped with sIg when sIg was cross-linked; 5) once loaded with Ag-antibody complexes, Fc gamma R also co-capped with sIg when sIg was sIg was cross-linked; 6) loading of Fc gamma R did not affect the co-capping of surface CR with cross-linked sIg and conversely, loading of CR did not affect the co-capping of Fc gamma R with cross-linked sIg; only loaded CR or Fc gamma R co-capped with sIg regardless of the status of the other surface molecule; 7) neither loaded nor free CR co-capped with cross-linked Fc gamma R, and neither loaded nor free Fc gamma R co-capped with cross-linked CR. These results demonstrate that both Fc gamma R and CR independently become associated with sIg when either receptor is loaded and sIg is cross-linked.

Animals↗

Human polyclonal and monoclonal IgG and IgM complement 3 nephritic factors: evidence for idiotypic commonality.

Complement 3 nephritic factors (C3NeF) were isolated from the sera of patients with membranoproliferative glomerulonephritis (MPGN) and the supernatants of pokeweed mitogen-stimulated mononuclear cells from patients with MPGN. Three human monoclonal C3NeF antibodies (two IgGs, CK and PH, and one IgM, K3C4) were established. Using an exhaustive series of affinity columns, we isolated anti-C3NeF idiotypic antibodies (anti-IdNeF) (three from normal and two from patient sera). Anti-IdNeF preparations bound to F(ab')2-NeF and prevented its ability to stabilize C3bBb convertase. We have used the above reagents to address questions on the genesis and the diversity of C3NeF antibodies. The following results were obtained: All anti-IdNeF preparations bound to C3NeF isolated from patient sera, cell culture supernatants, and IgG and IgM monoclonal C3NeF. None of the monoclonal C3NeF bound to an extensive battery of common antigens, including Fc portion of IgG, TNP, beta-galactosidase, DNA, and bacterial products. These data indicate that C3NeF express one common idiotype and that these antibodies are not raised in response to an obvious antigen.

Antibodies, Monoclonal↗

Use of adenine nucleotide derivatives to assess the potential of exo-active-site-directed reagents as species- or isozyme-specific enzyme inactivators. 3. Synthesis of adenosine 5'-triphosphate derivatives with N6- or 8-substituents bearing iodoacetyl groups.

Several series of N6- or 8-substituted derivatives of adenosine 5'-triphosphate (ATP) were synthesized. N6-(omega-Aminoalkyl) derivatives of adenosine 5'-monophosphate (AMP) were converted into their omega-N-carbobenzyloxy derivatives, and these were converted, via the 2',3'-O-carbonyl derivatives of their 5'-phosphorimidazolidates, into the corresponding ATP derivatives. Hydrogenolytic removal of the carbobenzyloxy groups, followed by iodoacetylation of the omega-amino groups with N-(iodoacetoxy)succinimide, gave N6-R-ATP, where R = (CH2)nNHCOCH2I (n = 2--8) or (CH2)nCON)CH3)(CH2)mN(CH3)CO(CH2)nNHCOCH2I (n = m = 3; n = 3, m = 4; n = 4, m = 3; n = m = 4). Condensation of N6-(omega-aminoalkyl) derivatives of AMP with N-hydroxysuccinimide esters of omega-[N-(carbobenzyloxy)amino] carboxylic acids gave N6-(CH2)nNHCO(CH2)mNH-Cbz derivatives of AMP which, upon conversion to the corresponding derivatives of ATP, followed by removal of the carbobenzyloxy group and iodoacetylation, as described above, gave N6-(CH2)nNHCO(CH2)mNHCOCH2I-ATP derivatives (n = 3, m = 5 or 6; n = 4, m = 5; n = 6, m = 1--6). The same sequence of reactions starting with N6-[omega-(methylamino)alkyl] derivatives of N6-CH3-AMP gave N6-CH3, N6-(CH2)nH(CH3)CO(CH2)mNHCOCH2I derivatives of ATP (n = 4, m = 3, 5 or 6; n = 6, m = 5 or 6). Reaction of alpha, omega-diaminoalkanes with 8-Br-ATP gave 8-NH(CH2)nNH2 derivatives of ATP, which upon iodoacetylation gave 8-NH(CH2)nNHCOCH2I derivatives of ATP (n = 2, 4, 6, or 8). Substrate and inhibitor properties indicated that the ATP derivatives are potential exco-ATP-site-directed inactivators of hexokinases, adenylate kinases, and pyruvate kinases.

Adenosine Diphosphate↗

Use of adenine nucleotide derivatives to assess the potential of exo-active-site-directed reagents as species- or isozyme-specific enzyme inactivators. 5. Interactions of adenosine 5'-triphosphate derivatives with rat pyruvate kinases, Escherichia coli thymidine kinase, and yeast and rat hexokinases.

Adenosine 5'-triphosphate (ATP) derivatives of the types N6-R-ATP [R = (CH2)nNHCOCH2I, (CH2)nNHCO-(CH2)mNHCOCH2I, or (CH2)nCON(Me)(CH2)mN(Me)CO(CH2)nNHCOCH2I], N6-Me-N6-R-ATP [R = (CH2)nN-(Me)CO(CH2)mNHCOCH2I], and 8-R-ATP [R = NM(CH2)nNHCOCH2I] with 5--19 spacer atoms between N6 or C-8 and iodine have been evaluated as potential exo-ATP-site-directed reagents for phosphokinases. Substrate and inhibitor properties indicated that the compounds possessed affinity for the ATP sites of the muscle (M), kidney (K), and liver (L) isozymes of rat pyruvate kinase (PK), of E. coli thymidine kinase (TK), and of yeast hexokinase (HK) and rat KH I, II, and III isozymes. Tests for time-dependent loss of enzyme activity (inactivation) were performed under conditions in which a large proportion of each phosphokinase was present as an enzyme-inhibitor complex. No ATP-site-directed inactivations resulted when the M, L, or K isozymes of PK were exposed for 8 h, 22 degrees C, to 5 mM levels of 18 ATP derivatives or 6 analogous ADP derivatives or when yeast HK or rat KH I, II, or III was exposed for 6 h, 22 degrees C, to 5 mM levels of 28 ATP derivatives. Escherichia coli TK was inactivated by 6 of 25 ATP derivatives tested at 10 mM, 6 h, 0 degrees C; inactivation was slowed by MgATP in the case of N6-CH3-N6-R-ATP [R = (CH2)4N(CH3)CO(CH2)5NHCOCH2I]. Only 1% of 298 enzyme-inhibitor combinations exhibited ATP-site-directed inactivation, signifying that few suitably positioned and sufficiently reactive nucleophilic groups were present near the enzymic ATP sites. Studies have now shown that exo-active-site-directed reagents can act as isozyme- or species-selective enzyme inhibitors. The present survey indicates that in many cases such reagents may be difficult of access when data are not available regarding structural or physicochemical features of the target enzyme adjacent to its catalytic site.

Adenosine Triphosphate↗

Formation of ribonucleotide 2',3'-cyclic carbonates during conversion of ribonucleoside 5'-phosphates to diphosphates and triphosphates by the phosphorimidazolidate procedure.

Ribo- and 2'-deoxyribonucleoside 5'-di- or triphosphates are commonly synthesized by reaction of inorganic phosphate or pyrophosphate with phosphorimidazolidates obtained by reaction of nucleoside 5'-phosphates with 1,1'-carbonyldiimidazole. The latter reaction, however, converted UMP, CMP, IMP, GMP, and AMP in high yield to the 2',3'-cyclic carbonate derivatives of their phosphorimidazolidates. Acidic treatment of the product from AMP gave AMP 2',3'-cyclic carbonate dihydrate; this was characterized by its uv, ir, and pmr spectra and by its conversion to adenosine 2',3'-cyclic carbonate by acid phosphatase and to AMP by basic hydrolysis. ADP or ATP synthesized by the phosphorimidazolidate method contained equal or greater amounts of their respective 2',3'-cyclic carbonates. The latter could be quantitatively converted to ADP and ATP, respectively, by 4-hr hydrolysis at pH 10.5, 22 degrees. ADP or ATP can be synthesized without concomitant 2',3'-cyclic carbonate formation by reaction of AMP with phosphorimidazolidates of inorganic phosphate or pyrophosphate.

Carbonates↗